Bioinformatic Analysis of Next Generation Sequencing Data from Cancer Cells

癌细胞下一代测序数据的生物信息学分析

• 批准号: 10005180
• 负责人: Elizabeth Thomas Bartom
• 金额: $ 17.4万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-19 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005180
• 关键词: Base Sequence; Big Data; Biochemistry; Bioinformatics; Biological; Biological Assay; Biology; Cancer Research Project; Cell Death; Cell physiology; Childhood Malignant Brain Tumor; Collaborations; Computational Biology; Computer Analysis; Data; Data Set; Development; Disease; Funding; Genetic Transcription; Goals; Histone H3; Histones; Lead; Malignant Childhood Neoplasm; Malignant Neoplasms; Methionine; Molecular; Molecular Genetics; Mutation; Proteins; Reproducibility; Research Personnel; Role; Transcriptional Elongation Factors; Universities; cancer cell; cancer type; chromatin protein; high standard; insight; leukemia; mutant; next generation sequencing; targeted cancer therapy; tumor progression

Project Summary This proposal supports the bioinformatics needs of two NCI funded Outstanding Investigators at the Northwestern University Department of Biochemistry and Molecular Genetics. One project, with Dr. Ali Shilatifard, examines the role of mutations in histone modifiers such as MLL in the progression of cancer. A recent discovery on the stabilization of mutant proteins relative to wildtype gives insight into one cause of disease and a new target for cancer therapy. Another project examines the role of transcription elongation factors in cancer development. These proteins are often fused to MLL in leukemia, but it is not clear why general transcriptional regulators lead to specific types of cancer. A third project examines another chromatin protein, histone H3, and how mutation of H3K27 to methionine can lead to specific types of pediatric brain cancer. Here too, new understanding of the molecular mechanism of the disease has led to a new line of therapy for this currently incurable and devastating childhood cancer. A fourth project, in collaboration with Dr. Marcus Peter, examines another fundamental cellular process, DISE, and how it might be exploited to trigger cell death specifically in cancer cells. The common thread in all of these projects is the need for careful, biologically motivated computational analysis to make sense of next generation sequencing data that is essential in examining the function of cancer cells, both before and after perturbation. Dr. Bartom will provide this analysis, and her expertise in both biology and computation will allow cancer biologists to extract more insight from their data, and to maintain a high standard of scientific rigor and reproducibility.

项目概要 该提案支持两位 NCI 资助的杰出研究人员的生物信息学需求 西北大学生物化学与分子遗传学系。与阿里博士合作的一个项目 Shilatifard 博士研究了组蛋白修饰剂（例如 MLL）突变在癌症进展中的作用。一个 最近关于突变蛋白相对于野生型的稳定性的发现使我们深入了解了导致这种现象的原因之一。 疾病和癌症治疗的新靶点。另一个项目研究转录延伸的作用 癌症发展的因素。这些蛋白质通常与白血病中的 MLL 融合，但尚不清楚原因 一般转录调节因子会导致特定类型的癌症。第三个项目检查另一种染色质 蛋白质、组蛋白 H3 以及 H3K27 突变为蛋氨酸如何导致儿童大脑的特定类型 癌症。在这里，对该疾病分子机制的新认识也催生了一条新的路线 治疗这种目前无法治愈且具有破坏性的儿童癌症。第四个项目是与博士合作的。 Marcus Peter 研究了另一个基本细胞过程 DISE，以及如何利用它来触发 细胞死亡，特别是癌细胞。所有这些项目的共同点是需要小心， 生物学驱动的计算分析，以理解下一代测序数据 对于检查扰动之前和之后癌细胞的功能至关重要。巴托姆博士将提供 这项分析以及她在生物学和计算方面的专业知识将使癌症生物学家能够提取更多信息 从数据中获得洞察力，并保持高标准的科学严谨性和可重复性。